Abstract
PRINS, a noncoding RNA identified earlier by our research group, contributes to psoriasis susceptibility and cellular stress response. We have now studied the cellular and histological distribution of PRINS by using in situ hybridization and demonstrated variable expressions in different human tissues and a consistent staining pattern in epidermal keratinocytes and in vitro cultured keratinocytes. To identify the cellular function(s) of PRINS, we searched for a direct interacting partner(s) of this stress-induced molecule. In HaCaT and NHEK cell lysates, the protein proved to be nucleophosmin (NPM) protein as a potential physical interactor with PRINS. Immunohistochemical experiments revealed an elevated expression of NPM in the dividing cells of the basal layers of psoriatic involved skin samples as compared with healthy and psoriatic uninvolved samples. Others have previously shown that NPM is a ubiquitously expressed nucleolar phosphoprotein which shuttles to the nucleoplasm after UV-B irradiation in fibroblasts and cancer cells. We detected a similar translocation of NPM in UV-B-irradiated cultured keratinocytes. The gene-specific silencing of PRINS resulted in the retention of NPM in the nucleolus of UV-B-irradiated keratinocytes; suggesting that PRINS may play a role in the NPM-mediated cellular stress response in the skin.
Highlights
Psoriasis is a multifactorial, hyperproliferative, chronic inflammatory skin disease that affects1%–3% of the adult Caucasian population (OMIM 177,900, www.ncbi.nlm.nih.gov), with a substantial negative impact on the patient’s quality of life [1]
We demonstrated earlier that PRINS, a noncoding RNA first identified by our research group, is expressed more strongly in the uninvolved psoriatic epidermis than in the psoriatic involved or healthy epidermis, suggesting that the overexpression of PRINS in the uninvolved psoriatic epidermis may play a role in psoriasis susceptibility
PRINS an RNA polymerase II transcribed RNA, is a 3681 nucleotide-long molecule. We originally described it in HaCaT keratinocytes where it participates in cellular stress response
Summary
Hyperproliferative, chronic inflammatory skin disease that affects. We demonstrated earlier that PRINS, (psoriasis susceptibility-related RNA gene induced by stress), a noncoding RNA (ncRNA) first identified by our research group, is expressed more strongly in the uninvolved psoriatic epidermis than in the psoriatic involved or healthy epidermis, suggesting that the overexpression of PRINS in the uninvolved psoriatic epidermis may play a role in psoriasis susceptibility. Our in vitro experiments revealed that PRINS functions as a regulatory RNA, playing a protective role in cells exposed to stress [13]. Since their first detection [14] numerous mRNA-like ncRNA transcripts have been found in different cell types. Our experiments indicate a similar pattern of intracellular localization of NPM after UV-B exposure in cultured keratinocytes, and reveal that the gene-specific silencing of PRINS modifies the UV-induced intracellular shuttling of NPM suggesting that NPM is a physical and functional interactor of PRINS
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